PDF (16.2 MB)
Collect
Submit Manuscript
Open Access

Soy polysaccharide maintains colonic homeostasis to protect from dextran sulphate sodium-induced colitis by modulating gut microbiota and intestinal epithelial regeneration

Nana ZhangaJianlin LiuaWeiyue ZhangaXinxin GuoaShuying LiaHongtai ZhangaMinjie WangbBei FanaFengzhong Wanga()
Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Key Laboratory of Agro-Products Processing, Ministry of Agriculture, Beijing 100095, China
School of Basic Medical Sciences, Inner Mongolia Medical University, Hohhot 010107, China

Peer review under responsibility of Tsinghua University Press.

Show Author Information

Abstract

Soy polysaccharide (SP) has been reported to possess the properties of modulating gut microbiome diversity. Here, we aimed to explore the protective effects of SP against dextran sulphate sodium (DSS)-induced colitis. Pre-treatment with SP at a dosage of 400 mg/kg·day alleviated colitis symptoms, preventing the weight loss and colon shorten. SP suppressed DSS-induced inflammatory response and enhanced M1 to M2 macrophage polarization. Further investigation showed that SP significantly promoted the regeneration of crypt and the expansion of goblet cell production. In addition, bacterial 16S rRNA sequencing analysis showed that SP modulated the composition of fecal microbiota, including selectively increasing Lactobacillus relative abundance. Notably, SP treatment enriched the production of Lactobacillus-derived lactic acid, which was sensed by its specific G-protein-coupled receptor 81 (Gpr81)/Wnt3/β-catenin signaling, and promoted the regeneration of intestinal stem cells. Fecal microbiome transplantation demonstrated that intestinal flora partially contributed to the beneficial effects of SP on preventing against colitis. In conclusion, SP exhibited the protective effects against colitis, which could be partly associated with modulating the composition of gut microbiota and enrichment of lactic acid. This study suggests that SP has potential to be developed as nutritional intervention to prevent colitis.

References

[1]

R.J. Xavier, D.K. Podolsky, Unravelling the pathogenesis of inflammatory bowel disease, Nature 448 (2007) 427-434. https://doi.org/10.1038/nature06005.

[2]

C. Burrello, F. Garavaglia, F.M. Cribiu, et al., Therapeutic faecal microbiota transplantation controls intestinal inflammation through IL10 secretion by immune cells, Nat. Commun. 9 (2018) 5184. https://doi.org/10.1038/s41467-018-07359-8.

[3]

Q. Hou, J. Huang, H. Ayansola, et al., Intestinal stem cells and immune cell relationships: potential therapeutic targets for inflammatory bowel diseases, Front. Immunol. 11 (2020) 623691. https://doi.org/10.3389/fimmu.2020.623691.

[4]

G. De Palma, M.D. Lynch, J. Lu, et al., Transplantation of fecal microbiota from patients with irritable bowel syndrome alters gut function and behavior in recipient mice, Sci. Transl. Med. 9 (2017). https://doi.org/10.1126/scitranslmed.aaf6397.

[5]

R.D.O. Carvalho, F.L.R. do Carmo, A. de Oliveira Junior, et al., Use of wild type or recombinant lactic acid bacteria as an alternative treatment for gastrointestinal inflammatory diseases: a focus on inflammatory bowel diseases and mucositis, Front. Microbiol. 8 (2017) 800. https://doi.org/10.3389/fmicb.2017.00800.

[6]

Y. Huang, J. Zhang, R. Dong, et al., Lactate as a metabolite from probiotic Lactobacilli mitigates ethanol-induced gastric mucosal injury: an in vivo study, BMC Complement. Med. Ther. 21 (2021) 26. https://doi.org/10.1186/s12906-020-03198-7.

[7]

P. Ranganathan, A. Shanmugam, D. Swafford, et al., GPR81, a cell-surface receptor for lactate, regulates intestinal homeostasis and protects mice from experimental colitis, J. Immunol. 200 (2018) 1781-1789. https://doi.org/10.4049/jimmunol.1700604.

[8]

Y.S. Lee, T.Y. Kim, Y. Kim, et al., Microbiota-derived lactate accelerates intestinal stem-cell-mediated epithelial development, Cell Host Microbe 24 (2018) 833-846 e6. https://doi.org/10.1016/j.chom.2018.11.002.

[9]

V. Singh, B.S. Yeoh, R.E. Walker, et al., Microbiota fermentation-NLRP3 axis shapes the impact of dietary fibres on intestinal inflammation, Gut 68 (2019) 1801-1812. https://doi.org/10.1136/gutjnl-2018-316250.

[10]

A. Redondo-Cuenca, M.J. Villanueva-Suarez, I. Mateos-Aparicio, Soybean seeds and its by-product okara as sources of dietary fibre. Measurement by AOAC and Englyst methods, Food Chem. 108 (2008) 1099-1105. https://doi.org/10.1016/j.foodchem.2007.11.061.

[11]

A. Nakamura, H. Furuta, H. Maeda, et al., Structural studies by stepwise enzymatic degradation of the main backbone of soybean soluble polysaccharides consisting of galacturonan and rhamnogalacturonan, Biosci. Biotechnol. Biochem. 66 (2002) 1301-1313. https://doi.org/10.1271/bbb.66.1301.

[12]

B. Le, T.N.A. Pham, S.H. Yang, Prebiotic potential and anti-inflammatory activity of soluble polysaccharides obtained from soybean residue, Foods 9 (2020) 1808. https://doi.org/10.3390/foods9121808.

[13]

M.S. Swallah, H. Fan, S. Wang, et al., Prebiotic impacts of soybean residue (Okara) on eubiosis/dysbiosis condition of the gut and the possible effects on liver and kidney functions, Molecules 26 (2021) 326. https://doi.org/10.3390/molecules26020326.

[14]

L. Yao, Z. Wang, H. Zhao, et al., Protective effects of polysaccharides from soybean meal against X-ray radiation induced damage in mouse spleen lymphocytes, Int. J. Mol. Sci. 12 (2011) 8096-8104. https://doi.org/10.3390/ijms12118096.

[15]

P. Chen, X. Chen, L. Hao, et al., The bioavailability of soybean polysaccharides and their metabolites on gut microbiota in the simulator of the human intestinal microbial ecosystem (SHIME), Food Chem. 362 (2021) 130233. https://doi.org/10.1016/j.foodchem.2021.130233.

[16]

S.N. Murthy, H.S. Cooper, H. Shim, et al., Treatment of dextran sulfate sodium-induced murine colitis by intracolonic cyclosporin, Dig. Dis. Sci. 38 (1993) 1722-1734. https://doi.org/10.1007/BF01303184.

[17]

D. Rachmilewitz, F. Karmeli, K. Takabayashi, et al., Immunostimulatory DNA ameliorates experimental and spontaneous murine colitis, Gastroenterology 122 (2002) 1428-1441. https://doi.org/10.1053/gast.2002.32994.

[18]

T.R. Wu, C.S. Lin, C.J. Chang, et al., Gut commensal Parabacteroides goldsteinii plays a predominant role in the anti-obesity effects of polysaccharides isolated from Hirsutella sinensis, Gut 68 (2019) 248-262. https://doi.org/10.1136/gutjnl-2017-315458.

[19]

R. Ungaro, S. Mehandru, P.B. Allen, et al., Ulcerative colitis, Lancet 389 (2017) 1756-1770. https://doi.org/10.1016/S0140-6736(16)32126-2.

[20]

A.C. Luissint, C.A. Parkos, A. Nusrat, Inflammation and the intestinal barrier: leukocyte-epithelial cell interactions, cell junction remodeling, and mucosal repair, Gastroenterology 151 (2016) 616-632. https://doi.org/10.1053/j.gastro.2016.07.008.

[21]

M. Alipour, D. Zaidi, R. Valcheva, et al., Mucosal barrier depletion and loss of bacterial diversity are primary abnormalities in paediatric ulcerative colitis, J. Crohns Colitis. 10 (2016) 462-471. https://doi.org/10.1093/ecco-jcc/jjv223.

[22]

Y. Yao, G. Kim, S. Shafer, et al., Mucus sialylation determines intestinal host-commensal homeostasis, Cell 185 (2022) 1172-1188.e28. https://doi.org/10.1016/j.cell.2022.02.013.

[23]

D. Taupin, D.K. Podolsky, Trefoil factors: initiators of mucosal healing, Nat. Rev. Mol. Cell Biol. 4 (2003) 721-732. https://doi.org/10.1038/nrm1203.

[24]

S. Cornick, M. Kumar, F. Moreau, et al., VAMP8-mediated MUC2 mucin exocytosis from colonic goblet cells maintains innate intestinal homeostasis, Nat. Commun. 10 (2019) 4306. https://doi.org/10.1038/s41467-019-11811-8.

[25]

B.A. Duerkop, M. Kleiner, D. Paez-Espino, et al., Murine colitis reveals a disease-associated bacteriophage community, Nat. Microbiol. 3 (2018) 1023-1031. https://doi.org/10.1038/s41564-018-0210-y.

[26]

A. Reyes, M. Wu, N.P. McNulty, et al., Gnotobiotic mouse model of phage-bacterial host dynamics in the human gut, PNAS 110 (2013) 20236-20241. https://doi.org/10.1073/pnas.1319470110.

[27]

R. Lucas Lopez, M.J. Grande Burgos, A. Galvez, et al., The human gastrointestinal tract and oral microbiota in inflammatory bowel disease: a state of the science review, APMIS 125 (2017) 3-10. https://doi.org/10.1111/apm.12609.

[28]

D. Gevers, S. Kugathasan, L.A. Denson, et al., The treatment-naive microbiome in new-onset Crohn's disease, Cell Host Microbe 15 (2014) 382-392. https://doi.org/10.1016/j.chom.2014.02.005.

[29]

A. Hirano, J. Umeno, Y. Okamoto, et al., Comparison of the microbial community structure between inflamed and non-inflamed sites in patients with ulcerative colitis, J. Gastroenterol. Hepatol. (2018). https://doi.org/10.1111/jgh.14129.

[30]

S.J. Ott, M. Musfeldt, D.F. Wenderoth, et al., Reduction in diversity of the colonic mucosa associated bacterial microflora in patients with active inflammatory bowel disease, Gut 53 (2004) 685-693. https://doi.org/10.1136/gut.2003.025403.

[31]

B. Sovran, J. Planchais, S. Jegou, et al., Enterobacteriaceae are essential for the modulation of colitis severity by fungi, Microbiome 6 (2018) 152. https://doi.org/10.1186/s40168-018-0538-9.

[32]

M.X. Byndloss, E.E. Olsan, F. Rivera-Chavez, et al., Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion, Science 357 (2017) 570-575. https://doi.org/10.1126/science.aam9949.

[33]

J.Y. Lee, S.A. Cevallos, M.X. Byndloss, et al., High-fat diet and antibiotics cooperatively impair mitochondrial bioenergetics to trigger dysbiosis that exacerbates pre-inflammatory bowel disease, Cell Host Microbe 28 (2020) 273-284 e6. https://doi.org/10.1016/j.chom.2020.06.001.

[34]

Q. Hou, L. Ye, H. Liu, et al., Lactobacillus accelerates ISCs regeneration to protect the integrity of intestinal mucosa through activation of STAT3 signaling pathway induced by LPLs secretion of IL-22, Cell Death Differ. 25 (2018) 1657-1670. https://doi.org/10.1038/s41418-018-0070-2.

[35]

H. Wu, S. Xie, J. Miao, et al., Lactobacillus reuteri maintains intestinal epithelial regeneration and repairs damaged intestinal mucosa, Gut Microbes 11 (2020) 997-1014. https://doi.org/10.1080/19490976.2020.1734423.

[36]

D. Ahl, H. Liu, O. Schreiber, et al., Lactobacillus reuteri increases mucus thickness and ameliorates dextran sulphate sodium-induced colitis in mice, Acta Physiol. 217 (2016) 300-310. https://doi.org/10.1111/apha.12695.

[37]

S. Sun, X. Xu, L. Liang, et al., Lactic acid-producing probiotic saccharomyces cerevisiae attenuates ulcerative colitis via suppressing macrophage pyroptosis and modulating gut microbiota, Front. Immunol. 12 (2021) 777665. https://doi.org/10.3389/fimmu.2021.777665.

[38]

T. Okada, S. Fukuda, K. Hase, et al., Microbiota-derived lactate accelerates colon epithelial cell turnover in starvation-refed mice, Nat. Commun. 4 (2013) 1654. https://doi.org/10.1038/ncomms2668.

[39]

S. Dong, M. Zhu, K. Wang, et al., Dihydromyricetin improves DSS-induced colitis in mice via modulation of fecal-bacteria-related bile acid metabolism, Pharmacol. Res. 171 (2021) 105767. https://doi.org/10.1016/j.phrs.2021.105767.

[40]

P.M. Miranda, G. De Palma, V. Serkis, et al., High salt diet exacerbates colitis in mice by decreasing Lactobacillus levels and butyrate production, Microbiome 6 (2018) 57. https://doi.org/10.1186/s40168-018-0433-4.

[41]

M.A. von Schillde, G. Hormannsperger, M. Weiher, et al., Lactocepin secreted by Lactobacillus exerts anti-inflammatory effects by selectively degrading proinflammatory chemokines, Cell Host Microbe. 11 (2012) 387-396. https://doi.org/10.1016/j.chom.2012.02.006.

[42]

C. Liu, J. Wu, J. Zhu, et al., Lactate inhibits lipolysis in fat cells through activation of an orphan G-protein-coupled receptor, GPR81, J. Biol. Chem. 284 (2009) 2811-2822. https://doi.org/10.1074/jbc.M806409200.

[43]

E. Khatib-Massalha, S. Bhattacharya, H. Massalha, et al., Lactate released by inflammatory bone marrow neutrophils induces their mobilization via endothelial GPR81 signaling, Nat. Commun. 11 (2020) 3547. https://doi.org/10.1038/s41467-020-17402-2.

[44]

K. Yang, J. Xu, M. Fan, et al., Lactate suppresses macrophage pro-inflammatory response to LPS stimulation by inhibition of YAP and NF-κB activation via GPR81-mediated signaling, Front. Immunol. 11 (2020) 587913. https://doi.org/10.3389/fimmu.2020.587913.

[45]

T. Sato, R.G. Vries, H.J. Snippert, et al., Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche, Nature 459 (2009) 262-265. https://doi.org/10.1038/nature07935.

[46]

T. Sato, J.H. van Es, H.J. Snippert, et al., Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts, Nature 469 (2011) 415-418. https://doi.org/10.1038/nature09637.

[47]

N. Barker, J.H. van Es, J. Kuipers, et al., Identification of stem cells in small intestine and colon by marker gene Lgr5, Nature 449 (2007) 1003-1007. https://doi.org/10.1038/nature06196.

[48]

T. Valenta, B. Degirmenci, A.E. Moor, et al., Wnt ligands secreted by subepithelial mesenchymal cells are essential for the survival of intestinal stem cells and gut homeostasis, Cell Rep. 15 (2016) 911-918. https://doi.org/10.1016/j.celrep.2016.03.088.

Food Science and Human Wellness
Pages 3284-3300
Cite this article:
Zhang N, Liu J, Zhang W, et al. Soy polysaccharide maintains colonic homeostasis to protect from dextran sulphate sodium-induced colitis by modulating gut microbiota and intestinal epithelial regeneration. Food Science and Human Wellness, 2024, 13(6): 3284-3300. https://doi.org/10.26599/FSHW.2023.9250015
Metrics & Citations  
Article History
Copyright
Rights and Permissions
Return